|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | Directors of the California stem cell agency today gave the go ahead to a $243 million disease team grant round aimed at generating a "development candidate" for a clinical trial, more than doubling the size of the original proposal by the CIRM staff.
The huge round would fund up to 30 planning grants and 12 full grants of up to $20 million. It would come on top of the initial disease team | | | | | | | | | | | | | | | | | | | | | | | | | The board meeting of the California stem cell agency began about 10 a.m. today. Currently speaking is CIRM President Alan Trounson, who is reviewing recent research involving stem cells. | | | | | | | | | | | | | | | | | | | | | | | | | The regulatory role of c-MYC on HDAC2 and PcG expression in human multipotent stem cells. J Cell Mol Med. 2010 Aug 16; Authors: Bhandari DR, Seo KW, Jung JW, Kim HS, Yang SR, Kang SK, Kang KS Abstract c-MYC is a well known nuclear oncoprotein having multiple functions in cell proliferation, apoptosis and cellular transformation. Chromosomal modification is also important to the differentiation and growth of stem cells. Histone Deacethylase (HDAC) and Polycomb group (PcG) family genes are well known chromosomal modification genes. The aim of this study was to elucidate the role of c-MYC in the expression of chromosomal modification via the HDAC family genes in human mesenchymal stem cells (hMSCs). To achieve this goal, c-MYC expression was modified by gene knock-down and over-expression via lentivirus vector. Using the modified c-MYC expression, our study was focused on cell proliferation, differentiation and cell cycle. Furthermore, the relationship of c-MYC with HDAC2 and PcG genes was also examined. The cell proliferation and differentiation were checked and shown to be dramatically decreased in c-MYC knocked-down human umbilical cord blood-derived MSCs (hUCB-MSCs), whereas they were increased in c-MYC over-expressing cells. Similarly, RT-PCR and Western Blotting results revealed that HDAC2 expression was decreased in c-MYC knocked-down and increased in c-MYC over-expressing hMSCs. Database indicates presence of c-MYC binding motif (CACGTG) in HDAC2 promoter region, which was confirmed by Chromatin immunoprecipitation (ChIP) assay. The influence of c-MYC and HDAC2 on PcG expression was confirmed. This might indicate the regulatory role of c-MYC over HDAC2 and PcG genes. c-MYCs' regulatory role over HDAC2 was also confirmed in human adipose tissue-derived MSCs (hAD-MSCs) and bone-marrow derived MSCs (hBM-MSCs). From this finding, it can be concluded that c-MYC plays a vital role in cell Proliferation & differentiation via chromosomal modification. PMID: 20716118 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Combined Technologies for Microfabricating Elastomeric Cardiac Tissue Engineering Scaffolds. Macromol Biosci. 2010 Aug 18; Authors: Guillemette MD, Park H, Hsiao JC, Jain SR, Larson BL, Langer R, Freed LE Polymer scaffolds that direct elongation and orientation of cultured cells can enable tissue engineered muscle to act as a mechanically functional unit. We combined micromolding and microablation technologies to create muscle tissue engineering scaffolds from the biodegradable elastomer poly(glycerol sebacate). These scaffolds exhibited well defined surface patterns and pores and robust elastomeric tensile mechanical properties. Cultured C2C12 muscle cells penetrated the pores to form spatially controlled engineered tissues. Scanning electron and confocal microscopy revealed muscle cell orientation in a preferential direction, parallel to micromolded gratings and long axes of microablated anisotropic pores, with significant individual and interactive effects of gratings and pore design. PMID: 20718054 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | New insights into induction of early-stage neovascularization in an improved tissue-engineered model of psoriasis. J Tissue Eng Regen Med. 2010 Aug 17; Authors: Krajewska E, Lewis C, Staton C, Macgowan A, Macneil S We have previously shown that putrescine induces a psoriatic phenotype in tissue-engineered skin. The initial aim of this study was to further develop this in vitro model by introducing endothelial cells to mimic the increased vascularization found in psoriasis. Human keratinocytes and fibroblasts, which did not express CD34 or CD31 in 2D culture, were added to de-epidermised acellular human dermis and cultured for 4 weeks. For induction of a psoriatic phenotype, putrescine was added during this period. We report that after 4 weeks of culture, and particularly when exposed to putrescine, this model showed expression of vertically organised clusters of CD31 positive cells in the dermis in the absence of any exogenous endothelial cells. Further investigation in 2D cell cultures showed an indirect effect of putrescine on normal keratinocytes causing them to produce soluble factors that increased expression of CD133, CD34 and CD31 in cultured human dermal fibroblasts, previously negative for these antigens. This study reports a new and improved model of psoriasis for in vitro studies and offers a new insight into early stage neovascularization, which is of relevance not only to psoriasis, but to tissue engineering and wound healing in general. Copyright (c) 2010 John Wiley & Sons, Ltd. PMID: 20718049 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Differential bone-forming capacity of osteogenic cells from either embryonic stem cells or bone marrow-derived mesenchymal stem cells. J Tissue Eng Regen Med. 2010 Aug 17; Authors: Both SK, van Apeldoorn AA, Jukes JM, Englund MC, Hyllner J, van Blitterswijk CA, de Boer J For more than a decade, human mesenchymal stem cells (hMSCs) have been used in bone tissue-engineering research. More recently some of the focus in this field has shifted towards the use of embryonic stem cells. While it is well known that hMSCs are able to form bone when implanted subcutaneously in immune-deficient mice, the osteogenic potential of embryonic stem cells has been mainly assessed in vitro. Therefore, we performed a series of studies to compare the in vitro and in vivo osteogenic capacities of human and mouse embryonic stem cells to those of hMSCs. Embryonic and mesenchymal stem cells showed all characteristic signs of osteogenic differentiation in vitro when cultured in osteogenic medium, including the deposition of a mineralized matrix and expression of genes involved in osteogenic differentiation. As such, based on the in vitro results, osteogenic ES cells could not be discriminated from osteogenic hMSCs. Nevertheless, although osteogenic hMSCs formed bone upon implantation, osteogenic cells derived from both human and mouse embryonic stem cells did not form functional bone, indicated by absence of osteocytes, bone marrow and lamellar bone. Although embryonic stem cells show all signs of osteogenic differentiation in vitro, it appears that, in contrast to mesenchymal stem cells, they do not possess the ability to form bone in vivo when a similar culture method and osteogenic differentiation protocol was applied. Copyright (c) 2010 John Wiley & Sons, Ltd. PMID: 20718035 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Temperature effects on type I pepsin-solubilised collagen extraction from silver-line grunt skin and its in vitro fibril self-assembly. J Sci Food Agric. 2010 Aug 17; Authors: Aukkanit N, Garnjanagoonchorn W BACKGROUND: Fish skin is a potential source of collagen. Increasing the extraction temperature increases the yield of collagen. However, it may also result in degradation of the peptide chains, thus damaging the 3D structure of collagen that is vital for its application as a biomaterial. This work investigated the effects of extraction temperature on the yield and characteristics, including fibril self-assembly, of type I pepsin-solubilised fish skin collagen.RESULTS: Pepsin-solubilised collagens were extracted from fresh skin of silver-line grunt at 4, 10, 20 and 28 degrees C for 6 h. Extraction at 10 degrees C gave the highest yield of collagens (439.32 +/- 96.43 mg g(-1) fresh skin, dry basis), which were identified as type I and comprised beta, alpha1 and alpha2 subunits. Extraction at higher temperatures (20 and 28 degrees C) resulted in the formation of low-molecular-weight peptide fragments, thus reducing the yield of the resultant type I collagen. The denaturation temperatures of collagens extracted at 4 and 10 degrees C, as determined by thermal analysis using differential scanning calorimetry, were 39.5 and 37.5 degrees C respectively. In vitro fibril self-assembly of 1 mg mL(-1) collagen solution (pH 6) incubated at 25 degrees C was only observed with collagens extracted at 4 and 10 degrees C. The 10 degrees C collagen not only showed a higher rate of self-assembly, but its matrix also had a larger fibril diameter of 0.50 +/- 0.07 microm (compared with 0.41 +/- 0.07 microm for the 4 degrees C collagen) after 4 h of incubation.CONCLUSION: The results indicated strong effects of extraction temperature on the yield and characteristics of the collagen obtained. Extraction of pepsin-solubilised collagen from silver-line grunt skin at 4-10 degrees C gave a high yield of type I collagen with molecular integrity suitable for tissue-engineering applications. Copyright (c) 2010 Society of Chemical Industry. PMID: 20718032 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Defining conditions for covalent immobilization of angiogenic growth factors onto scaffolds for tissue engineering. J Tissue Eng Regen Med. 2010 Aug 17; Authors: Chiu LL, Weisel RD, Li RK, Radisic M Rapid vascularization of engineered tissues in vitro and in vivo remains one of the key limitations in tissue engineering. We propose that angiogenic growth factors covalently immobilized on scaffolds for tissue engineering can be used to accomplish this goal. The main objectives of this work were: (a) to derive desirable experimental conditions for the covalent immobilization of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1) on porous collagen scaffolds; and (b) to determine whether primary endothelial cells respond to these scaffolds with covalently immobilized angiogenic factors. VEGF and Ang1 were covalently immobilized onto porous collagen scaffolds, using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) chemistry. To improve covalent immobilization conditions: (a) different reaction buffers [phosphate-buffered saline (PBS), distilled water, or 2-(N-morpholino)ethanesulphonic acid (MES)] were used; and (b) step immobilization was compared to bulk immobilization. In step immobilization, growth factors are applied after EDC activation of the scaffold, while in bulk immobilization, reagents are simultaneously applied to the scaffold. PBS as the reaction buffer resulted in higher amounts of VEGF and Ang1 immobilized (ELISA), higher cell proliferation rates (XTT) and increased lactate metabolism compared to water and MES as the reaction buffers. Step immobilization in PBS buffer was also more effective than bulk immobilization. Immobilized growth factors resulted in higher cell proliferation and lactate metabolism compared to soluble growth factors used at comparable concentrations. Tube formation by CD31-positive cells was also observed in collagen scaffolds with immobilized VEGF or Ang1 using H5V and primary rat aortic endothelial cells but not on control scaffolds. Copyright (c) 2010 John Wiley & Sons, Ltd. PMID: 20717888 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Evaluation of alginate hydrogels under in vivo-like bioreactor conditions for cartilage tissue engineering. J Mater Sci Mater Med. 2010 Aug 18; Authors: Stojkovska J, Bugarski B, Obradovic B Alginate hydrogels in forms of discs and packed beds of microbeads (~800 mum) were tested in a novel bioreactor at 10% strain using two regimes: at a loading rate of 337.5 mum/s and at sequential increments of 50 mum displacement every 30 min. Compressive strength increased with the increase in alginate concentration (1.5 vs. 2% w/w) and the content of guluronic residues (38.5 vs. 67%). Packed beds of microbeads exhibited significantly higher (~1.5-3.4 fold) compression moduli than the respective discs indicating the effects of gel form and entrapped water. Short-term cultivation of microbeads with immobilized bovine calf chondrocytes (1.5% w/w, 33 x 10(6) cells/ml) under biomimetic conditions (dynamic compression: 1 h on/1 h off, 0.42 Hz, 10% strain) resulted in cell proliferation and bed compaction, so that the compression modulus slightly increased. Thus, the novel bioreactor demonstrated advantages in evaluation of biomaterial properties and cell-biomaterial interactions under in vivo-like settings. PMID: 20717710 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Current strategies for knee cartilage repair. Int J Clin Pract. 2010 Sep;64(10):1444-52 Authors: Kalson NS, Gikas PD, Briggs TW Defects in knee articular cartilage (AC) can cause pain and disability and present the clinician with an extremely challenging clinical situation. This article describes the most up-to-date surgical techniques that aim to repair and/or regenerate symptomatic focal defects in AC, which include arthroscopic debridement, microfracture bone marrow stimulation and autologous osteochondral allografting, with an emphasis on autologous chondrocyte implantation. In the future, refinement of tissue-engineering approaches promises to further improve outcome for these patients. PMID: 20716151 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Survival and function of mesenchymal stem cells (MSCs) depend on glucose to overcome exposure to long-term, severe and continuous hypoxia. J Cell Mol Med. 2010 Aug 16; Authors: Deschepper M, Oudina K, David B, Myrtil V, Collet C, Bensidhoum M, Logeart-Avramoglou D, Petite H Abstract Use of mesenchymal stem cells (MSCs) has emerged as a potential new treatment for various diseases but has generated marginally successful results. A consistent finding of most studies is massive death of transplanted cells. The present study examined the respective roles of glucose and continuous severe hypoxia on MSC viability and function in pertinent to bone tissue engineering. We hereby demonstrate for the first time that MSC survive exposure to long-term (12 day), severe (pO(2)< 1.5 mmHg) hypoxia provided that glucose is available. To this aim, an in vitro model that mimics the hypoxic environment and cell-driven metabolic changes encountered by grafted sheep cells was established. In this model, the hallmarks of hypoxia (low pO(2), HIF-1alpha expression and anaerobic metabolism) were present. When conditions switched from hypoxic (low pO(2)) to ischemic (low pO(2) and glucose depletion), MSCs exhibited shrinking, decreased cell viability and ATP content due to complete exhaustion of glucose at day 6; these results provided evidence that ischemia led to the observed massive cell death. Moreover, MSCs exposed to severe, continuous hypoxia, but without any glucose shortage, remained viable and maintained both their in vitro proliferative ability after simulation with blood reperfusion at day 12 and their in vivo osteogenic ability. These findings challenge the traditional view according to which severe hypoxia per se is responsible for the massive MSC death observed upon transplantation of these cells and provide evidence that MSC are able to withstand exposure to severe, continuous hypoxia provided that a glucose supply is available. PMID: 20716129 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Uncultured marrow mononuclear cells delivered within fibrin glue hydrogels to porous scaffolds enhance bone regeneration within critical size rat cranial defects. Tissue Eng Part A. 2010 Aug 17; Authors: Kretlow JD, Spicer PP, Jansen J, Vacanti CA, Kasper FK, Mikos AG For bone tissue engineering, the benefits of incorporating mesenchymal stem cells (MSCs) into porous scaffolds are well established. There is, however, little consensus on the effects of or need for MSC handling ex vivo. Culture and expansion of MSCs adds length, cost, and likely increases risk associated with treatment. We evaluated the effect of using uncultured bone marrow mononuclear cells (bmMNCs) encapsulated within fibrin glue hydrogels and seeded into porous scaffolds to regenerate bone over 12 weeks in an 8 mm diameter, critical size rat cranial defect. A full factorial experimental design was used to evaluate bone formation within model poly(L-lactic acid) and corraline hydroxyapatite scaffolds with or without platelet rich plasma (PRP) and bmMNCs. Mechanical push-out testing, microcomputed tomographical (microCT) analyses, and histology were performed. PRP showed no benefit for bone formation. Cell-laden PLLA scaffolds without PRP required significantly greater force to displace from surrounding tissues than control (cell-free) scaffolds, but no differences were observed during push out testing of coral scaffolds. For bone volume formation as analyzed by microCT, significant positive overall effects were observed with bmMNC incorporation. These data suggest that bmMNCs may provide therapeutic advantages in bone tissue engineering applications without the need for culture, expansion, and purification. PMID: 20715884 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Technologies for cardiac valve prostheses] Kyobu Geka. 2009 Jul;62(8 Suppl):692-8 Authors: Nakano K To show the technological development of cardiac valve prostheses, a historical review of both mechanical and biological valve prostheses and a current overview of modern cardiac valve devices are provided. Scince the 1st implantation of Starr-Edwards ball valve in 1960, both mechanical and biological valve prostheses have advanced. The valve design, the material of the leaflet and the hausing of mechanical prostheses have improved. Currently, the majority of the mechanical prostheses are bileaflet tilting disc valves made of pyrolytic carbon, which is antithromboembolic. However, anticoagulation therapy with warfarin is still required. As for the bioprostheses, although the fixation and anti-mineralization methods of the tissues improved, the durability of these valves is still limited. For the material of the current biological valves, the porcine aortic valve or bovine pericardium are used. The tissues are fixed by non-pressure or low-pressure method in glutaraldehyde solution. A stented and non-stented valves are available. Epoch-making events in this field are the implantation of new bioprosthetic valves using tissue engineering methods and the development of the transcatheter valve replacement therapies. PMID: 20715694 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Subtalar joint arthrodesis, ankle arthrodiastasis, and talar dome resurfacing with the use of a collagen-glycosaminoglycan monolayer. Clin Podiatr Med Surg. 2010 Apr;27(2):327-33 Authors: Ramanujam CL, Sagray B, Zgonis T Intraarticular fractures of the calcaneus are a common injury to the hindfoot leading to posttraumatic arthrosis of the subtalar joint. Operative treatment with reduction and internal fixation at the time of initial presentation and once the soft tissue envelope is deemed suitable has become the standard of care for the surgical management of calcaneal fractures. However, numerous complications have been associated with calcaneal fractures, most notably subtalar joint arthrosis and calcaneal malunion. The authors describe a method of a delayed subtalar joint arthrodesis, ankle joint arthrodiastasis, and talar resurfacing with positive results for the management of painful posttraumatic concomitant arthrosis of the subtalar and ankle joints. PMID: 20470961 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Salivary gland regeneration. Front Oral Biol. 2010;14:107-28 Authors: Carpenter GH, Cotroneo E The ability of animal salivary glands to recover from an experimentally-induced atrophic state offers hope that human salivary glands may be regenerated following injury. Examination of the mechanisms of regeneration in animal models has revealed processes which resemble the embryonic formation of salivary glands. Secretory proteins present in regenerated acinar and ductal cells are the same as found in the perinatal salivary glands. The use of microarrays to reveal global gene changes has, in combination with bioinformatic techniques, identified some of the important signalling cascades operating in the early stages of glandular regeneration. The role of stem cells is also considered and would fit in with current ideas of glandular regeneration, however the isolation and subsequent differentiation of stem cells into a normal reflexly secreting gland still requires considerable research. PMID: 20428014 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Tracheal defect repair using a PLGA-collagen hybrid scaffold reinforced by a copolymer stent with bFGF-impregnated gelatin hydrogel. Pediatr Surg Int. 2010 Jun;26(6):575-80 Authors: Tatekawa Y, Kawazoe N, Chen G, Shirasaki Y, Komuro H, Kaneko M PURPOSE: We studied the regenerated cartilage in tracheal defect repair and compared the bio-materials used versus native trachea using basic fibroblast growth factor (bFGF)-impregnated gelatin hydrogel. MATERIALS AND METHODS: A full-thickness anterior defect was created in the cervical trachea of 15 experimental rabbits. The defect was implanted with a hybrid scaffold of poly(lactic-co-glycolic acid) (PLGA) knitted mesh and collagen sponge. The implanted trachea was reinforced with a copolymer stent of polycaprolactone and poly(lactic acid) coarse fiber mesh. A gelatin hydrogel was used for providing a sustained release of bFGF. The reconstructed tracheas were divided into three groups with wrapped materials; without gelatin hydrogel (control group, n = 5), a gelatin hydrogel with saline (gelatin group, n = 5), and a gelatin hydrogel with 100 microg of bFGF (bFGF group, n = 5). One of the five rabbits in each group at 1 month after operation, one at 3 months, and three at 6 months were killed and the engineered tracheas were evaluated histologically. Biomechanical properties were evaluated on samples at 6 months postoperatively. RESULTS: The rigid support in the defect portion was maintained during 6 months postoperatively. The newly regenerated cartilages were recognized between the host cartilage stumps at 3 months postoperatively in the bFGF group, and limited new cartilage growth and epithelialization were observed at 6 months postoperatively. CONCLUSIONS: The experiment shows that using bFGF, better mechanical strength was obtained but with poor cartilage growth. PMID: 20425118 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Regulating a master regulator: Establishing tissue-specific gene expression in skeletal muscle. Epigenetics. 2010 Nov 16;5(8) Authors: Aziz A, Liu QC, Dilworth FJ MyoD is a master regulator of the skeletal muscle gene expression program. ChIP-Seq analysis has recently revealed that MyoD binds to a large number of genomic loci in differentiating myoblasts, yet only activates transcription at a subset of these genes. Here we discuss recent data suggesting that the ability of MyoD to mediate gene expression is regulated through the function of Polycomb and Trithorax Group proteins. Based on studies of the muscle-specific myog gene, we propose a model where the transcriptional activators Mef2d and Six4 mediate recruitment of Trithorax Group proteins Ash2L/MLL2 and UTX to MyoD-bound promoters to overcome the Polycomb-mediated repression of muscle genes. Modulation of the interaction between Ash2L/MLL2 and Mef2d by the p38alpha MAPK signaling pathway in turns provides fine-tuning of the muscle-specific gene expression program. Thus Mef2d, Six4 and p38alpha MAPK function coordinately as regulators of a master regulator to mediate expression of MyoD target genes. PMID: 20716948 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Phase II trial of bevacizumab and erlotinib in patients with recurrent malignant glioma. Neuro Oncol. 2010 Aug 17; Authors: Sathornsumetee S, Desjardins A, Vredenburgh JJ, McLendon RE, Marcello J, Herndon JE, Mathe A, Hamilton M, Rich JN, Norfleet JA, Gururangan S, Friedman HS, Reardon DA Vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) signaling are established contributors to malignant glioma (MG) biology. We, therefore, evaluated bevacizumab, a humanized anti-VEGF monoclonal antibody, in combination with the EGFR tyrosine kinase inhibitor erlotinib, in this phase 2 study for recurrent MG patients (www.ClinicalTrials.gov, NCT00671970). Fifty-seven patients (n = 25, glioblastoma [GBM]; n = 32, anaplastic glioma [AG]) were enrolled. The primary endpoint was 6-month progression-free survival (PFS-6). Overall survival (OS), radiographic response, pharmacokinetics, and correlative biomarkers were the secondary endpoints. Patients were stratified based on the concurrent use of enzyme-inducing antiepileptic drugs (EIAEDs). Bevacizumab (10 mg/kg) was given intravenously every 2 weeks. Erlotinib was orally administered daily at 200 mg/day for patients not on EIAEDs and 500 mg/day for patients on EIAEDs. PFS-6 and median OS were 28% and 42 weeks for GBM patients and 44% and 71 weeks for AG patients, respectively. Twelve (48%) GBM patients and 10 (31%) AG patients achieved a radiographic response. Erlotinib pharmacokinetic exposures were comparable between EIAED and non-EIAED groups. Rash, mucositis, diarrhea, and fatigue were common but mostly grades 1 and 2. Among GBM patients, grade 3 rash, observed in 32%, was associated with survival benefit, whereas elevated hypoxia-inducible factor-2 alpha and VEGF receptor-2 levels were associated with poor survival. Bevacizumab plus erlotinib was adequately tolerated in recurrent MG patients. However, this regimen was associated with similar PFS benefit and radiographic response when compared with other historical bevacizumab-containing regimens. PMID: 20716591 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Evolving paradigms for repair of tissues by adult stem/progenitor cells (MSCs). J Cell Mol Med. 2010 Aug 16; Authors: Prockop DJ, Kota DJ, Bazhanov N, Reger RL Abstract In this review we focus on the adult stem/progenitor cells that were initially isolated from bone marrow and first referred to as colony forming units-fibroblastic(see 1), then as marrow stromal cells(2), and subsequently as either mesenchymal stem cells(3) or multipotent mesenchymal stromal cells (MSCs)(4). The current interest in MSCs and similar cells from other tissues is reflected in over 10,000 citations in PubMed as of this writing with 5 to 10 new publications per day. It is also reflected in over 100 registered clinical trials with MSCs or related cells (http//www.clinicaltrials.gov). As a guide to the vast literature, this review will attempt to summarize many of the publications in terms of three paradigms that have directed much of the work (Figure 1): an initial paradigm that the primary role of the cells was to form niches for hematopoietic stem cells (Paradigm I); a second paradigm that the cells repaired tissues by engraftment and differentiation to replace injured cells (Paradigm II); and the more recent paradigm that MSCs engage in cross-talk with injured tissues and thereby generate microenvironments or "quasi-niches" that enhance the repair tissues (Paradigm III). PMID: 20716123 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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